Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation

Abstract

CD40 was originally described as a functionally significant B cell surface molecule. However, CD40 is also expressed on monocytes, dendritic cells, epithelial cells, and basophils. We now report that synovial membrane (SM) or dermal fibroblasts also express cell surface CD40 in vitro. Fibroblast CD40 expression declines with increasing time in culture and recombinant interferon-gamma (rINF-gamma) induces fibroblast CD40 up-regulation. This effect of rINF-gamma is augmented by recombinant interleukin-1 alpha or recombinant tumor necrosis factor-alpha. CD40 expression on fibroblasts is functionally significant because CD40L-CD40 interactions induce SM fibroblast CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1) up-regulation. Moreover, ligation of CD40 augments IL-6 production by SM fibroblasts and induces fibroblasts to proliferate. In addition, rINF-gamma enhances the effect of CD40L-CD40 interactions on fibroblast proliferation. Taken together, these studies show that fibroblasts can express CD40, cytokines can regulate fibroblast CD40 expression, and CD40 ligation induces fibroblast activation and proliferation.

Epstein – Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-κB pathway involving TNF receptor-associated factors

“…The IL6 promoter contains NF-kB sites and is under dominant control by this transcription factor following TNF treatment (Libermann and Baltimore, 1990;Shimizu et al, 1990). CD40 has also been shown to mediate IL6 secretion (Clark & Shu, 1990;Hess et al, 1995;Yellin et al, 1995), however the molecular events leading to this e ect are unclear.…”

The role of CD40/CD154 interactions in the priming, differentiation, and effector function of helper and cytotoxic T cells

“…Studies have suggested the functional expression of CD40 on T cells as well [5,6]. Stromal cells that express CD40 include thymic epithelia [7], vascular endothelium [8,9], keratinocytes [10,11], and fibroblasts [12]. Receptor expression is constitutive on B cells [13] and can be further up-regulated by interferon-␥ (IFN-␥) [1].…”

Augmented production of chemokines by the interaction of type II collagen–reactive T cells with rheumatoid synovial fibroblasts

“…CD40 ligand is expressed on activated T cells, and CD40 is expressed on FLS (37). Ligation of CD40 on FLS induces proliferation of FLS and upregulation of adhesion molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (23,38). Moreover, this interaction enhanced the production of cytokines, including IL-6 and vascular endothelial growth factor, by FLS (24,38).…”

“…Ligation of CD40 on FLS induces proliferation of FLS and upregulation of adhesion molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (23,38). Moreover, this interaction enhanced the production of cytokines, including IL-6 and vascular endothelial growth factor, by FLS (24,38). We therefore treated cocultures with neutralizing antibodies to CD40, which reduced the increments in chemokine production by 55-72%.…”